Pirfenidone therapy and inducers of cytochrome p450

Abstract

The present invention relates to methods involving avoiding adverse drug interactions with pirfenidone and CYP inducers, such as smoking.

What is claimed is: 
     
         1 . Pirfenidone for use in treating a patient in need of pirfenidone therapy, characterized in that the treating comprises avoiding or discontinuing concomitant use or co-administration of a strong inducer of cytochrome P450 1A2 (CYP1A2) to avoid reduced exposure to pirfenidone. 
     
     
         2 . The use of pirfenidone in the manufacture of a medicament for treating a patient in need of pirfenidone therapy, characterized in that the treating comprises avoiding or discontinuing concomitant use or co-administration of a strong inducer of cytochrome P450 1A2 (CYP1A2) to avoid reduced exposure to pirfenidone. 
     
     
         3 . A method of administering pirfenidone therapy to a patient in need thereof comprising administering to the patient a therapeutically effective amount of pirfenidone and avoiding or discontinuing a strong inducer of a cytochrome P450 1A2 (CYP1A2) to avoid reduced exposure to pirfenidone. 
     
     
         4 . The pirfenidone, use, or method of any one of  claims 1  to  3  comprising avoiding concomitant use or co-administration of a strong inducer of cytochrome P450 1A2 (CYP1A2). 
     
     
         5 . The pirfenidone, use, or method of any one of  claims 1  to  3  comprising discontinuing a strong inducer of cytochrome P450 1A2 (CYP1A2) prior to or concurrent with starting pirfenidone therapy to avoid reduced exposure to pirfenidone. 
     
     
         6 . The pirfenidone, use, or method of any one of  claims 1  to  3  wherein the patient is a smoker who is discontinuing smoking to avoid reduced exposure to pirfenidone. 
     
     
         7 . The pirfenidone, use, or method of  claim 6  wherein the patient is discontinuing smoking within 4 weeks prior to the administration of pirfenidone. 
     
     
         8 . The pirfenidone, use, or method of  claim 7  wherein the patient is discontinuing smoking concurrent with the start of administration of pirfenidone. 
     
     
         9 . The pirfenidone, use, or method of any one of  claims 1  to  3  wherein the patient is a smoker and avoids smoking when using pirfenidone. 
     
     
         10 . The pirfenidone, use, or method of any one of  claims 1  to  5  wherein the inducer of a CYP1A2 is rifampin. 
     
     
         11 . The pirfenidone, use, or method of any one of  claims 1  to  10  wherein the patient has idiopathic pulmonary fibrosis. 
     
     
         12 . The pirfenidone, use, or method of any one of  claims 1  to  11  wherein the patient suffers from a disease selected from pulmonary fibrosis, idiopathic pulmonary fibrosis, idiopathic interstitial pneumonia, autoimmune lung diseases, benign prostate hypertrophy, coronary or myocardial infarction, atrial fibrillation, cerebral infarction, myocardiac fibrosis, musculoskeletal fibrosis, post-surgical adhesions, liver cirrhosis, renal fibrotic disease, fibrotic vascular disease, scleroderma, Hermansky-Pudlak syndrome, neurofibromatosis, Alzheimer's disease, diabetic retinopathy, or skin lesions, lymph node fibrosis associated with HIV, chronic obstructive pulmonary disease (COPD), inflammatory pulmonary fibrosis, rheumatoid arthritis; rheumatoid spondylitis; osteoarthritis; gout, other arthritic conditions; sepsis; septic shock; endotoxic shock; gram-negative sepsis; toxic shock syndrome; myofacial pain syndrome (MPS); Shigellosis; asthma; adult respiratory distress syndrome; inflammatory bowel disease; Crohn's disease; psoriasis; eczema; ulcerative colitis; glomerular nephritis; scleroderma; chronic thyroiditis; Grave's disease; Ormond's disease; autoimmune gastritis; myasthenia gravis; autoimmune hemolytic anemia; autoimmune neutropenia; thrombocytopenia; pancreatic fibrosis; chronic active hepatitis including hepatic fibrosis; acute or chronic renal disease; renal fibrosis; diabetic nephropathy; irritable bowel syndrome; pyresis; restenosis; cerebral malaria; stroke or ischemic injury; neural trauma; Alzheimer's disease; Huntington's disease; Parkinson's disease; acute or chronic pain; allergies, including allergic rhinitis or allergic conjunctivitis; cardiac hypertrophy, chronic heart failure; acute coronary syndrome; cachexia; malaria; leprosy; leishmaniasis; Lyme disease; Reiter's syndrome; acute synoviitis; muscle degeneration, bursitis; tendonitis; tenosynoviitis; herniated, ruptured, or prolapsed intervertebral disk syndrome; osteopetrosis; thrombosis; silicosis; pulmonary sarcosis; bone resorption diseases, such as osteoporosis or multiple myeloma-related bone disorders; cancer, including but not limited to metastatic breast carcinoma, colorectal carcinoma, malignant melanoma, gastric cancer, or non-small cell lung cancer; graft-versus-host reaction; or auto-immune diseases, such as multiple sclerosis, lupus or fibromyalgia; AIDS or other viral diseases such as Herpes Zoster, Herpes Simplex I or II, influenza virus, Severe Acute Respiratory Syndrome (SARS) or cytomegalovirus; or diabetes mellitus, proliferative disorders (including both benign or malignant hyperplasias), acute myelogenous leukemia, chronic myelogenous leukemia, Kaposi's sarcoma, metastatic melanoma, multiple myeloma, breast cancer, including metastatic breast carcinoma; colorectal. carcinoma; malignant melanoma; gastric cancer; non-small cell lung cancer (NSCLC); bone metastases; pain disorders including neuromuscular pain, headache, cancer pain, dental pain, or arthritis pain; angiogenic disorders including solid tumor angiogenesis, ocular neovascularization, or infantile hemangioma; conditions associated with the cyclooxygenase or lipoxygenase signaling pathways, including conditions associated with prostaglandin endoperoxide synthase-2 (including edema, fever, analgesia, or pain); organ hypoxia; thrombin-induced platelet aggregation; or protozoal diseases. 
     
     
         13 . The pirfenidone, use, or method of any one of  claims 1  to  12  wherein the pirfenidone is administered at a total daily dosage of at least 1800 mg. 
     
     
         14 . The pirfenidone, use, or method of  claim 13  wherein the pirfenidone is administered at a total daily dosage of 2400 mg or 2403 mg. 
     
     
         15 . The pirfenidone, use, or method of any one of  claims 1  to  14 , wherein each dose of pirfenidone administered is 801 mg. 
     
     
         16 . The pirfenidone, use, or method of any one of  claims 1  to  15 , wherein pirfenidone is administered three times a day. 
     
     
         17 . The pirfenidone, use, or method of any one of  claims 1  to  16 , wherein pirfenidone is administered with food. 
     
     
         18 . A package or kit comprising (a) pirfenidone, optionally in a container, and (b) a package insert, package label, instructions or other labeling comprising avoiding or discontinuing concomitant use or co-administration of a strong inducer of cytochrome P450 1A2 (CYP1A2), and optionally according to any of the embodiments of  claims 1 - 17 .